chr1-150577397-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182763.3(MCL1):​c.783G>A​(p.Trp261*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

MCL1
NM_182763.3 stop_gained

Scores

1
9
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.11
Variant links:
Genes affected
MCL1 (HGNC:6943): (MCL1 apoptosis regulator, BCL2 family member) This gene encodes an anti-apoptotic protein, which is a member of the Bcl-2 family. Alternative splicing results in multiple transcript variants. The longest gene product (isoform 1) enhances cell survival by inhibiting apoptosis while the alternatively spliced shorter gene products (isoform 2 and isoform 3) promote apoptosis and are death-inducing. [provided by RefSeq, Oct 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MCL1NM_021960.5 linkc.1031G>A p.Gly344Asp missense_variant Exon 3 of 3 ENST00000369026.3 NP_068779.1 Q07820-1
MCL1NM_182763.3 linkc.783G>A p.Trp261* stop_gained Exon 2 of 2 NP_877495.1 Q07820-2
MCL1NM_001197320.2 linkc.572G>A p.Gly191Asp missense_variant Exon 4 of 4 NP_001184249.1 Q07820C8YZ26A0A087WT64

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MCL1ENST00000369026.3 linkc.1031G>A p.Gly344Asp missense_variant Exon 3 of 3 1 NM_021960.5 ENSP00000358022.2 Q07820-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Uncertain
0.16
D
BayesDel_noAF
Uncertain
-0.010
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.12
T;D
Eigen
Benign
0.17
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.74
T;T
MetaRNN
Benign
0.34
T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Uncertain
0.74
T
PROVEAN
Uncertain
-3.1
.;D
REVEL
Benign
0.21
Sift
Uncertain
0.0030
.;D
Sift4G
Uncertain
0.055
T;D
Polyphen
1.0
.;D
Vest4
0.57
MutPred
0.41
.;Loss of catalytic residue at G342 (P = 0.1222);
MVP
0.56
MPC
1.7
ClinPred
0.94
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.50
gMVP
0.80

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-150549873; API